During the past few years a body of literature has developed around a type of compound known as ACE inhibitors; i.e., compounds which intervene in the angiotensinogen (renin).fwdarw.angiotensin I.fwdarw.(ACE).fwdarw.angiotensin II sequence by inhibiting angiotensin converting enzyme (ACE) and reducing or eliminating the formation of the pressor substance angiotensin II. These compounds can be described generally as mercaptoacyl amino acids. Exemplary references describing these compounds are set forth, infra., under the heading "Detailed Description of the Invention".
The most well known of the mercaptoacyl amino acid ACE inhibitors is captopril, the chemical name of which is (S)-1-(3-mercapto-2-methyl-1-oxopropyl)-L-proline. Belgian Pat. No. 873,092 published June 27, 1979 describes pharmaceutical compositions comprising captopril in combination with a variety of diuretics.
Bicking et al., J. Med. Chem., 19:530 (1976) discuss the formation of adducts from (diacylvinylaryloxy)acetic acids and mercaptoacetic acid. These adducts, like the parent compounds, are said to have diuretic activity. Further discussion of these adducts can be found in an article by Bormann in Chemistry in Britain, 15:72 (1979). The author suggests that the adducts function as prodrugs.